Serotonin Syndrome — Management Pathway

Step-by-step decision

Choose step by step as prompted; reaching an endpoint gives the management recommendation. You can go back a step or restart anytime.

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Full pathway

1. [Decision] Hunter criteria
   Do the Hunter criteria fit (serotonergic drug + neuromuscular signs)? (Rapid onset (<24 h) after a serotonergic drug (SSRI/SNRI/MAOI/tramadol/linezolid/triptan/MDMA, etc.). Hunter criteria: drug + one of — 1) spontaneous clonus; 2) inducible clonus + agitation or diaphoresis; 3) ocular clonus + agitation or diaphoresis; 4) tremor + hyperreflexia; 5) hypertonia + temperature >38°C + ocular or inducible clonus. Clonus/hyperreflexia (lower-limb predominant) are the key discriminators (NMS has rigidity/hyporeflexia).)
   • Hunter criteria met (serotonin syndrome) → Confirmed → stop drug + support
   • Not met / consider NMS, etc. → Not met
2. [End] Not met
   Differentiate NMS (dopamine antagonist, lead-pipe rigidity, onset over days), anticholinergic toxicity, malignant hyperthermia, thyroid storm, meningoencephalitis, etc., and manage along the appropriate pathway.
3. [End] Confirmed → stop drug + support
   1) Immediately stop all serotonergic drugs (the core measure). 2) Support: fluids, active cooling, ECG monitoring. 3) Benzodiazepines for agitation/myoclonus (first-line sedation). 4) Moderate–severe add cyproheptadine (a 5-HT2A antagonist, oral/NG). 5) Severe (temperature >41.1°C, rigidity, respiratory failure): intubate + non-depolarizing paralysis (rocuronium, not succinylcholine) + active cooling; antipyretics do not work. Usually resolves within 24 h of stopping the drug.

Source guidelines & references

• Hunter Serotonin Toxicity Criteria (Dunkley 2003); serotonin syndrome management

This pathway is our own synthesis of the decision logic in the guidelines above (not the guideline verbatim); thresholds and workflows change as guidelines update — in practice follow the latest guideline, your institution's protocol and the individual patient.

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